Skip to comments.MicroRNA in TLR signaling and endotoxin tolerance
Posted on 08/17/2011 3:05:14 PM PDT by neverdem
Toll-like receptors (TLRs) in innate immune cells are the prime cellular sensors for microbial components. TLR activation leads to the production of proinflammatory mediators and thus TLR signaling must be properly regulated by various mechanisms to maintain homeostasis. TLR4-ligand lipopolysaccharide (LPS)-induced tolerance or cross-tolerance is one such mechanism, and it plays an important role in innate immunity. Tolerance is established and sustained by the activity of the microRNA miR-146a, which is known to target key elements of the myeloid differentiation factor 88 (MyD88) signaling pathway, including IL-1 receptor-associated kinase (IRAK1), IRAK2 and tumor-necrosis factor (TNF) receptor-associated factor 6 (TRAF6). In this review, we comprehensively examine the TLR signaling involved in innate immunity, with special focus on LPS-induced tolerance. The function of TLR ligand-induced microRNAs, including miR-146a, miR-155 and miR-132, in regulating inflammatory mediators, and their impact on the immune system and human diseases, are discussed. Modulation of these microRNAs may affect TLR pathway activation and help to develop therapeutics against inflammatory diseases.
Innate immunity is the first line defense mechanism that recognizes, responds to and resolves invading pathogens or their conserved molecular patterns that are common to broad pathogen classes, commonly known as pathogen-associated molecular patterns (PAMPs). For the past few decades, there has been an incredible expansion in our understanding of the molecular components of innate immunity and their physiological function in host defense.1 Recognition of microorganisms is linked to a chain of events that promote inflammation, activation of innate immune responses and priming of adaptive immune responses. During microbial invasion, danger signals are effectively detected through several families of innate immune receptors. These receptors collectively survey the extracellular space, endolysosomal compartments and cytoplasm for signs of infection or tissue damage. The specificities of these receptors are fixed in the germline and are able to recognize a...
(Excerpt) Read more at nature.com ...
It’s a FReebie, but you may have to register - not subscribe - at Nature.
Can you give me a gist of what makes this paper so interesting? Most FReepers are not microbiologists.
As these receptors have a central role in linking pathogen recognition to the induction of innate immunity, inflammation and eventually adaptive immunity, understanding the regulation of the signaling cascade is important.
Thus, it will be interesting to study the functional consequence of miRNA expression both in vivo and in vitro during bacterial infection and the mechanism through which they affect innate immunity. It remains to be determined whether dysregulation of miRNAs is causal to the development and progression of inflammatory diseases. Finally, revealing the modest regulation of TLR signaling by miRNAs will provide promising drug discovery targets against various inflammatory diseases.
Knowledge of these pathways increases the ‘targets’ of drug discovery.
It is also cool because the RNA itself is effecting a change.
Usually DNA-> RNA -> Functional protein. And the functional protein does all the cool stuff with signal transduction, gene activation, etc, etc.
This is cool because it is DNA -> functional RNA.
It's an open access recent review article of basic immunology. Iimmunology and microbiology are complimentary fields. Physicians need to understand this stuff too. Some are just science junkies.
aruanan & allmendream, thanks for pitching in!